Secondary cell wall polymers of Enterococcus faecalis are critical for resistance to complement activation via mannose-binding lectin

Download
  1. Get@NRC: Secondary cell wall polymers of Enterococcus faecalis are critical for resistance to complement activation via mannose-binding lectin (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1074/jbc.M112.358283
AuthorSearch for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for:
TypeArticle
Journal titleJournal of Biological Chemistry
ISSN0021-9258
1083-351X
Volume287
Issue45
Pages3776937777; # of pages: 9
SubjectBacterial Pathogenesis; Cell Wall; Immunology; Innate Immunity; Polysaccharide; Enterococcus faecalis; Complement System; Mannose-binding Lectin; Teichoic Acid
AbstractThe complement system is part of our first line of defense against invading pathogens. The strategies used by Enterococcus faecalis to evade recognition by human complement are incompletely understood. In this study, we identified an insertional mutant of the wall teichoic acid (WTA) synthesis gene tagB in E. faecalis V583 that exhibited an increased susceptibility to complement-mediated killing by neutrophils. Further analysis revealed that increased killing of the mutant was due to a higher rate of phagocytosis by neutrophils, which correlated with higher C3b deposition on the bacterial surface. Our studies indicated that complement activation via the lectin pathway was much stronger on the tagB mutant compared with wild type. In concordance, we found an increased binding of the key lectin pathway components mannose-binding lectin and mannose-binding lectin-associated serine protease-2 (MASP-2) on the mutant. To understand the mechanism of lectin pathway inhibition by E. faecalis, we purified and characterized cell wall carbohydrates of E. faecalis wild type and V583ΔtagB. NMR analysis revealed that the mutant strain lacked two WTAs with a repeating unit of →6)[α-L-Rhap-(1→3)]β-D-GalpNAc-(1→5)-Rbo-1-P and →6) β-D-Glcp-(1→3) [α-D-Glcp-(1→4)]-β-D-GalpNAc-(1→5)-Rbo-1-P→, respectively (Rbo, ribitol). In addition, compositional changes in the enterococcal rhamnopolysaccharide were noticed. Our study indicates that in E. faecalis, modification of peptidoglycan by secondary cell wall polymers is critical to evade recognition by the complement system.
Publication date
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
NPARC number21269083
Export citationExport as RIS
Report a correctionReport a correction
Record identifier77515935-04bd-4412-9a81-9e728fd6465c
Record created2013-12-05
Record modified2016-05-09
Bookmark and share
  • Share this page with Facebook (Opens in a new window)
  • Share this page with Twitter (Opens in a new window)
  • Share this page with Google+ (Opens in a new window)
  • Share this page with Delicious (Opens in a new window)
Date modified: